Examining Solution and Solid State Composition for the Solution-Mediated Polymorphic Transformation of Carbamazepine and Piracetam

Abstract

Solution-mediated polymorphic transformations (SMPT) of the pharmaceutical compounds carbamazepine and piracetam have been investigated. Seeded transformation experiments were performed, and the solution concentration was monitored by in situ infrared spectroscopy using a calibration free method. Solid samples were also taken over time, and the percentage of metastable and stable polymorphic phases were determined using off line quantitative powder X-ray diffraction analysis. Solution and solid state data were compared for each compound. In the case of carbamazepine, the SMPT from FI to FIII was identified as being controlled by the growth of the stable FIII polymorph. For piracetam, the SMPT was also identified as being controlled by growth of the stable polymorph, but with a more considerable induction time for nucleation of the stable phase. This paper demonstrates how the rate determining steps of the SMPT can be identified if both solution and solid phase data are recorded. The results are compared with other studies reported in the literature and rationalized into four principal scenarios.